PROJECT SUMMARY/ABSTRACT In the United States, it is estimated that one-third of all new HIV diagnoses are among people less than 25 years of age. There is strong evidence that adherence to ART is a primary determinant of virological suppression, disease progression, and mortality. However, a recent review and meta- analysis of research on youth with HIV found an average ART adherence rate of 53% in North America, the lowest adherence rate globally. Intensive and/or in-person adherence intervention models have been problematic for youth with HIV. Interventions requiring multiple visits, even with brief, in-person sessions, have been difficult for youth to complete. These models have largely failed to promote long-term, sustained medication adherence (and sustained viral load below detection), and are commonly cost prohibitive for use in real world settings regardless of efficacy. Given these issues, one possibility for sustainable, yet individualized intervention delivery is through mobile health/technology-based approaches. This proposal directly addresses the urgent need for culturally acceptable, youth-friendly ART adherence interventions that can be rapidly implemented in clinical settings. We plan to conduct a clinical trial comparing two promising youth-friendly intervention strategies: weekday cell phone support (CPS) and daily text messaging (SMS). In pilot studies, both have demonstrated significant improvements in medication adherence. Participants who received CPS showed significant reductions in HIV viral load during the 24 week intervention; moreover, effects persisted for 24 weeks post intervention. The proposed research moves beyond a traditional clinical trial by utilizing a ?SMART? (Sequential Multiple Assignment Randomized Trial) design as a cost-effective and methodologically rigorous way to explore additional questions to optimize the interventions and maximize clinical utility and real-world implementation. This SMART design will allow us to identify the most effective and cost efficient sequence of SMS and/or CPS, utilizing incentives strategically, and tapering to sustain the impact of the intervention. We hypothesize that youth randomized to CPS will have significantly greater viral load suppression (primary outcome) and self-reported medication adherence (secondary outcome) than those in the SMS group. The proposed research brings together a team of skilled HIV clinical and behavioral researchers with decades of experience with clinical care and adherence research with youth, including numerous collaborations within the NIH-funded Adolescent Trials Network. This research will be conducted at five clinical sites with decades of experience conducting trials and that have a track record of excellence in recruiting, retaining, and collecting data from youth living with HIV.